N-Phenylisoxazolidin-5-one derivatives may be used as intermediates in the preparation of β-amino acid esters, which can be further converted into other biologically important compounds, for example, β-amino acids. β-Amino acids possess biologically important properties, occur in natural products, and are the building blocks to several bioactive compounds.
The preparation of N-phenylisoxazolidin-5-one derivatives may involve carbon-nitrogen (C—N) bond forming reactions. Catalytic methods for C—N bond formation have been reported and have been applied in organic synthesis, including in the preparation of pharmaceuticals and natural products.
Organocatalytic reactions for forming C—N bonds are of interest, as these reactions may avoid the use of toxic and/or expensive metal catalysts. Examples of organocatalytic C—N bond formation reactions, including proline-catalyzed direct α-aminations of carbonyl compounds, have been reported. N-Nitroso aldol reaction of enamines selectively forming N-hydroxyaminoketones have also been reported (see, for example, Yamamoto, H. and Momiyama, N. J. Am. Chem. Soc. 2005, 127, 1080; Momiyama, N.; Yamamoto, Y.; Yamamoto, H. J. Am. Chem. Soc. 2007, 129, 1190). The enantioselective conjugate addition of N-silyloxycarbamates to enals using imidazolidinone catalysts has been used to obtain enantio-enriched β-amino aldehydes. The reaction of enals and N-protected hydroxylamine in the presence of chiral pyrrolidine catalysts, forming 5-hydroxyisoxazolidines that are further converted to the corresponding β-amino acids or γ-amino alcohols, has been reported.
In addition to C—N bond formation, organocatalytic reactions for forming carbon-carbon (C—C) bonds have been reported. For example, NHC-catalyzed activation of carbonyl compounds has been reported as a potential method for metal-free C—C bond forming reactions via the nucleophilic “Breslow intermediate”, or the homoenolate equivalent species (see, for example, Sohn, S. S.; Rosen, E. L.; Bode, J. F. J. Am. Chem. Soc. 2004, 126, 14370; Burstein, C. and Glorius, F. Angew. Chem., Int. Ed. 2004, 43, 6205). The ability of thiamine-dependent enzymes to convert aromatic nitroso compounds into hydroxamic acids has been reported.
Additional approaches to synthesizing N-phenylisoxazolidin-5-one derivatives and β-amino acid ester derivatives involving readily available reactants and catalysts are desirable.